Publications

2021

Shroff S, Gu S, Vardhan S A, Mani I, Aziz K, P N, Datta D, Friedman D. Screening first-degree relatives of glaucoma patients reveals barriers to participation. Br J Ophthalmol. 2021;
PURPOSE: To report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India. METHODS: 1598 glaucoma patients were contacted via letter or letter and phone call and asked to bring their siblings and children to a glaucoma screening. Participants underwent standardised eye examinations and completed questionnaires that assessed barriers to participation and awareness of glaucoma risk. Two-proportion z-tests were used to compare categorical data. Costs associated with the screening were recorded. RESULTS: 206 probands (12.9%) attended the screening along with 50 siblings and children. Probands were nearly twice as likely to attend if they had been contacted via both letter and phone call rather than letter only. Over half of probands reported that their relatives could not participate because they did not live in the region, and one-fifth reported that their relatives had other commitments. Fifty-eight per cent of the siblings and children who attended did not know that they were at increased risk for glaucoma due to their family history, and 32.0% did not know that the relative who had invited them to the screening had glaucoma. Thirteen siblings and children (26.0% of those who attended) were found to have findings concerning for glaucoma. The average cost per first-degree relative who was screened was INR2422 (£26). CONCLUSION: Participation in this glaucoma screening campaign was poor. The major barrier to participation was distance from the screening site and associated indirect costs. Better strategies for bringing first-degree relatives in for examinations are needed.
Peng C, Wang Y, Ji L, Kuang L, Yu Z, Li H, Zhang J, Zhao J. LncRNA-MALAT1/miRNA-204-5p/Smad4 Axis Regulates Epithelial-Mesenchymal Transition, Proliferation and Migration of Lens Epithelial Cells. Curr Eye Res. 2021;46(8):1137–1147.
MATERIALS AND METHODS: LECs were cultured and induced with TGF-β2 (10 ng/mL). SiRNA against MALAT1 (Si-MALAT1) was transfected into LECs to knockdown the expression of MALAT1. To overexpress or knockdown miR-204-5p, miR-204-5p mimics (miR-204-5p mimics) and anti-miR-204-5p (miR-204-5p inhibitor) were transfected into LECs. We used RNA FISH to identify the location of MALAT1. RNA levels of MALAT1 and miR-204-5p were analyzed by RT-qPCR. Additionally, target protein levels of Smad4, epithelial differentiation and mesenchymal markers were analyzed with Western blot. We employed EdU Labeling to measured cell proliferation and performed Transwell Assay to analyze the cell migration. Dual-luciferase reporter assays in LECs were conducted to verify whether miRNA-204-5p was negatively regulated by MALAT1 and Smad4 was a direct target of miR-204-5p. RESULTS: The expression of MALAT1 was upregulated in PCO specimens. MALAT1 was overexpressed in TGF-β2 induced LECs, and the knockdown of MALAT1 could attenuate TGF-β2 induced EMT. Besides, the upregulation of MALAT1 was correlated with the downregulation of miR-204-5p and upregulation of Smad4. Importantly, MALAT1 was revealed to be located in the cytoplasm of LECs. Furthermore, luciferase reporter assays confirmed that MALAT1 could negatively regulate the expression of miR-204-5p and then regulate its direct target Smad4. Finally, the knockdown of MALAT1 could inhibit the EMT, proliferation, and migration of LECs; however, those can be reversed by anti-miR-204-5p. CONCLUSIONS: Our findings reveal that MALAT1 may regulate EMT, proliferation, and migration of LECs as a ceRNA by "sponging" miR-204-5p and targeting Smad4, and serve as a promising therapeutic target in preventing PCO.
Morrison D, Binenbaum G, Chang M, Heidary G, Trivedi R, Galvin J, Pineles S. Office- or Facility-Based Probing for Congenital Nasolacrimal Duct Obstruction: A Report by the American Academy of Ophthalmology. Ophthalmology. 2021;128(6):920–927.
PURPOSE: To review the published literature assessing the efficacy and safety of in-office probing compared with facility-based probing to treat congenital nasolacrimal duct obstruction (NLDO). METHODS: Literature searches were conducted in March 2020 in the PubMed database with no date restrictions and limited to studies published in English and in the Cochrane Library database with no restrictions. The combined searches yielded 281 citations. Of these, 21 articles were deemed appropriate for inclusion in this assessment and assigned a level of evidence rating by the panel methodologist. Four articles were rated level I, 2 articles were rated level II, and 15 articles were rated level III. RESULTS: Treatments consisted of observation, in-office nasolacrimal probing, or facility-based nasolacrimal probing. Success rates and complications or recurrences were recorded from 1 week to 6 months after surgery. Complete resolution of symptoms after surgery ranged from 66% to 95.6% for office-based procedures versus 50% to 97.7% for facility-based procedures. Level I evidence indicated that 66% of cases spontaneously resolved after 6 months of observation in infants between 6 and 10 months of age. Success rates for in-office probing were lower for bilateral than for unilateral NLDO (67% vs. 82%), whereas success rates were high in both unilateral (83%) and bilateral (82%) patients who underwent facility-based probing after 6 months of observation. Cost data did not indicate a definitive cost savings of either treatment method ($562 for in-office vs. $701 for facility-based, depending on cost models predicting spontaneous resolution rates at different ages). No serious adverse events with treatment or anesthesia were reported for either treatment method. CONCLUSIONS: Evidence supports the efficacy and safety of both in-office and facility-based surgery for congenital NLDO. However, treating bilateral NLDO in a facility setting may be better. Because a significant percentage of children achieved resolution spontaneously before 12 months of age, deferring treatment until 12 to 18 months of age is a reasonable option. Additional research may address symptom burden on families and the impact of anesthesia and emotional trauma of nonsedated office probings on patients and may explore further the cost of treatment for each treatment method.
Krawitz B, Sirinek P, Doobin D, Nanda T, Ghiassi M, Horowitz J, Liebmann J, De Moraes C. The Challenge of Managing Bilateral Acute Angle-closure Glaucoma in the Presence of Active SARS-CoV-2 Infection. J Glaucoma. 2021;30(3):e50-e53.
PURPOSE: To report a case of bilateral acute angle-closure glaucoma associated with hyponatremia in the setting of chlorthalidone use and SARS-CoV-2 infection, and to demonstrate the challenges of managing this patient given her infectious status. METHODS: This was a case report. CASE: A 65-year-old woman taking chlorthalidone for hypertension presented to the emergency room with headache, pain, and blurry vision in both eyes and was found to be in bilateral acute angle closure. On laboratory investigation, she was severely hyponatremic and also tested positive for SARS-CoV-2. B-scan ultrasound demonstrated an apparent supraciliary effusion in the right eye. Following stabilization of her intraocular pressures with medical management, she ultimately underwent cataract extraction with iridectomies and goniosynechiolysis in both eyes. CONCLUSIONS: We report a rare case of bilateral acute angle-closure glaucoma associated with hyponatremia. Chlorthalidone use and perhaps SARS-CoV-2 infection may have contributed to this electrolyte abnormality and unique clinical presentation. In addition, we discuss the challenges of managing this complex patient with active SARS-CoV-2 infection during the pandemic.
Ung L, Jonas J, Lietman T, Chodosh J. COVID-19 and the Unfinished Agenda of VISION 2020. Am J Ophthalmol. 2021;224:30–35.
PURPOSE: To critically evaluate the potential impact of the coronavirus disease (COVID-19) pandemic on global ophthalmology and VISION 2020. DESIGN: Perspective supplemented with epidemiologic insights from available online databases. METHODS: We extracted data from the Global Vision Database (2017) and Global Burden of Disease Study (2017) to highlight temporal trends in global blindness since 1990, and provide a narrative overview of how COVID-19 may derail progress toward the goals of VISION 2020. RESULTS: Over 2 decades of VISION 2020 advocacy and program implementation have culminated in a universal reduction of combined age-standardized prevalence of moderate-to-severe vision impairment (MSVI) across all world regions since 1990. Between 1990 and 2017, low-income countries observed large reductions in the age-standardized prevalence per 100,000 persons of vitamin A deficiency (25,155 to 19,187), undercorrected refractive disorders (2,286 to 2,040), cataract (1,846 to 1,690), onchocerciasis (5,577 to 2,871), trachoma (506 to 159), and leprosy (36 to 26). Despite these reductions, crude projections suggest that more than 700 million persons will experience MSVI or blindness by 2050, principally owing to our growing and ageing global population. CONCLUSIONS: Despite the many resounding successes of VISION 2020, the burden of global blindness and vision impairment is set to reach historic levels in the coming years. The impact of COVID-19, while yet to be fully determined, now threatens the hard-fought gains of global ophthalmology. The postpandemic years will require renewed effort and focus on vision advocacy and expanding eye care services worldwide.
Jafari A, Sneidern M, Lehmann A, Shen S, Shishido S, Freitag S, Bleier B. Exclusively endoscopic endonasal resection of benign orbital tumors: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2021;11(5):924–934.
BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) classification system was developed to standardize prospective outcome analysis following orbital cavernous hemangioma (OCH) resection. The goal of this study was to retroactively apply the CHEER system to all prior existing reports of endoscopic resection of primary benign orbital tumors (BOTs) to: (1) compare patient presentations, perioperative characteristics, and outcomes between OCH and other BOTs; and (2) determine whether the CHEER categorization regime could be expanded to other BOTs. METHODS: A systematic review of studies reporting exclusively endoscopic resections of OCH and other BOTs (eg, solitary fibrous tumor, schwannoma, and meningioma) was performed. Patient, tumor characteristics, and operative outcomes were recorded. All tumors with adequate reporting were retrospectively assigned a CHEER stage. Outcomes were compared using chi-square or Fisher's exact tests. RESULTS: Ninety-three studies met inclusion criteria, and sufficient data were available in 36 studies, comprising 105 tumors (n = 87 OCHs; n = 18 other BOTs). Baseline patient and tumor characteristics, as well as intraoperative and short-term postoperative outcomes were not significantly different between OCHs and other BOTs. Long-term outcomes (eg, visual deficits, diplopia, eye position, and recurrence) also did not differ when controlling for CHEER stage. CONCLUSION: This review represents the largest collection of outcomes data following exclusively endoscopic endonasal resection of BOTs. Short-term and long-term outcomes appear similar between OCHs and other BOTs. These results suggest that exclusively endoscopic resection of orbital tumors may be effective in a range of benign pathologies. Furthermore, these results support a broader application of the CHEER system to other benign primary orbital tumors.
Choi EY, Li D, Fan Y, Pasquale L, Shen L, Boland M, Ramulu P, Yousefi S, De Moraes CG, Wellik S, Myers J, Bex P, Elze T, Wang M. Predicting Global Test-Retest Variability of Visual Fields in Glaucoma. Ophthalmol Glaucoma. 2021;4(4):390–399.
PURPOSE: To model the global test-retest variability of visual fields (VFs) in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Test-retest VFs from 4044 eyes of 4044 participants. METHODS: We selected 2 reliable VFs per eye measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm 24-2) within 30 days of each other. Each VF had fixation losses (FLs) of 33% or less, false-negative results (FNRs) of 20% or less, and false-positive results (FPRs) of 20% or less. Stepwise linear regression was applied to select the model best predicting the global test-retest variability from 3 categories of features of the first VF: (1) base parameters (age, mean deviation, pattern standard deviation, glaucoma hemifield test results, FPR, FNR, and FL); (2) total deviation (TD) at each location; and (3) computationally derived archetype VF loss patterns. The global test-retest variability was defined as root mean square deviation (RMSD) of TD values at all 52 VF locations. MAIN OUTCOME MEASURES: Archetype models to predict the global test-retest variability. RESULTS: The mean ± standard deviation of the root mean square deviation was 4.39 ± 2.55 dB. Between the 2 VF tests, TD values were correlated more strongly in central than in peripheral VF locations (intraclass coefficient, 0.66-0.89; P < 0.001). Compared with the model using base parameters alone (adjusted R2 = 0.45), adding TD values improved prediction accuracy of the global variability (adjusted R2 = 0.53; P < 0.001; Bayesian information criterion [BIC] decrease of 527; change of >6 represents strong improvement). Lower TD sensitivity in the outermost peripheral VF locations was predictive of higher global variability. Adding archetypes to the base model improved model performance with an adjusted R2 of 0.53 (P < 0.001) and lowering of BIC by 583. Greater variability was associated with concentric peripheral defect, temporal hemianopia, inferotemporal defect, near total loss, superior peripheral defect, and central scotoma (listed in order of decreasing statistical significance), and less normal VF results and superior paracentral defect. CONCLUSIONS: Inclusion of archetype VF loss patterns and TD values based on first VF improved the prediction of the global test-retest variability than using traditional global VF indices alone.
Kim J, Aschard H, Kang J, Lentjes MA, Do R, Wiggs J, Khawaja A, Pasquale L, Collaboration MRFG. Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank. Ophthalmology. 2021;128(6):866–876.
PURPOSE: We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP. DESIGN: Cross-sectional study in the UK Biobank. PARTICIPANTS: We included 121 374 participants (baseline ages, 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009-2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls). METHODS: We evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP. MAIN OUTCOME MEASURES: Intraocular pressure and glaucoma. RESULTS: Mendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P > 0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (≥232 mg/day) versus lowest (<87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (Ptrend = 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming > 480 mg/day versus < 80 mg/day was associated with a 0.35-mmHg higher IOP (Pinteraction = 0.01). The relationship between caffeine intake and glaucoma was null (P ≥ 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ≥ 321 mg/day showed a 3.90-fold higher glaucoma prevalence (Pinteraction = 0.0003). CONCLUSIONS: Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence.
Fickweiler W, Wolfson E, Paniagua S, Yu MG, Adam A, Bahnam V, Sampani K, Wu IH, Musen G, Aiello L, Shah H, Sun J, King G. Association of Cognitive Function and Retinal Neural and Vascular Structure in Type 1 Diabetes. J Clin Endocrinol Metab. 2021;106(4):1139–1149.
CONTEXT: Cognitive dysfunction is a growing and understudied public health issue in the aging type 1 diabetic population and is difficult and time-consuming to diagnose. Studies in long duration type 1 diabetes have reported the presence of proliferative diabetic retinopathy was associated with cognitive dysfunction. OBJECTIVE: This study assessed whether structural and vascular abnormalities of the retina, representing an extension of the central nervous system, are associated with cognitive impairment and other complications of type 1 diabetes. METHODS: An observational cross-sectional study of individuals with 50 or more years of type 1 diabetes (Joslin Medalist Study) was conducted at a university hospital in the United States. The study included 129 participants with complete cognitive testing. Validated cognitive testing measures included psychomotor speed, and immediate, and delayed memory. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed to obtain neural retinal layer thicknesses and vascular density for superficial (SCP) and deep retinal capillary plexus (DCP). Multivariable modeling was adjusted for potential confounders associated with outcomes in unadjusted analyses. RESULTS: Decreased vessel density of the SCP and DCP was associated with worse delayed memory (DCP: P = .002) and dominant hand psychomotor speed (SCP: P = .01). Thinning of the retinal outer nuclear layer was associated with worse psychomotor speed both in nondominant and dominant hands (P = .01 and P = .05, respectively). Outer plexiform layer thickness was associated with delayed memory (P = .04). CONCLUSION: These findings suggest that noninvasive retinal imaging using OCT and OCTA may assist in estimating the risks for cognitive dysfunction in people with type 1 diabetes.